This invention relates to an acetalsulfonate derivative, a process for producing the same, and a process for producing a styrene oxide derivative using an acetalsulfonate derivative or a mandelic acid derivative as a starting material.
The starting materials, intermediates and final products of this invention can also be optically active substances. The compounds obtained according to this invention are useful as raw materials for medicines, agricultural chemicals, and the like and further, can give, in good yield, styrene oxide derivatives and ethanolamine derivatives which are useful as raw materials for medicines, agricultural chemicals, and the like.
The acetalsulfonate derivative of this invention can be easily converted into the corresponding styrene oxide derivative by epoxidation. The styrene oxide derivative thus obtained can be converted into corresponding ethanolamine derivatives by a reaction with various amines.
With regard to a process for producing an acetalsulfonate derivative, there can be considered, for example, a process which comprises converting an ethanediol derivative into a sulfonate derivative, followed by protection with an acetal. This process, however, has a problem in that it has a poor selectivity in converting an ethanediol derivative into a sulfonate derivative and hence an intended product cannot be isolated in high yield (J. Org. Chem., 21, 1260 (1956))
As to a process for producing a styrene oxide derivative, there is well known a process which comprises epoxidizing a 2-hydroxy-2-phenylethyl sulfonate derivative or a 2-hydroxy-2-phenylethyl halide derivative by use of a base (J. Org. Chem. 21,597 (1956)).
However, the 2-hydroxy-2-phenylethyl sulfonate derivative or the 2-hydroxy-2-phenylethyl halide derivative which are the materials used in the above-mentioned process are difficult to obtain in high purity. Accordingly, the epoxidation reaction has previously been conducted by using, as such, the above-mentioned derivatives mingled with their positional isomers, i.e., a 2-hydroxy-1-phenylethyl sulfonate derivative or 2-hydroxy-1-phenylethyl halide derivative, and a disulfonate derivative or dihalide derivative (Synthesis, 1985,983) (U.S. Pat. No. 4391826). In this process, when disulfoante derivative or dihalide derivative is mingled into the starting material, it is apt to cause difficulty in purification of the product, resulting in lowering of the yield. Still, when a position isomer is mingled, though the process has no problem in producing a racemic substance, it is apt to cause lowering of optical purity in case an optically active substance is produced.
Although an acetalsulfonate derivative and styrene oxide derivative are useful as an intermediate for medicines and agricultural chemicals, previous processes for producing them have problems as described above. Accordingly, a development of an industrial process for producing the derivatives has been eagerly awaited which is highly safe, simple and economical and gives good yield.
The present inventors have made extensive studies to achieve the above-mentioned object. As the result, the inventors have found that an acetalsulfonate derivative can be produced in high purity and high yield by using an inexpensive mandelic acid derivative as a starting material and that a styrene oxide derivative can be produced in high purity and high yield by using an acetalsulfonate derivative or a mandelic acid derivative as a starting material. This invention has been attained on the basis of the above finding.
Thus, the first aspect of this invention relates to an acetalsulfonate derivative which is represented by the following formula (1) 
wherein R1 and R2 can be same as or different from each other and each denote a hydrogen atom, halogen atom, hydroxyl group, a straight or branched chain alkyl group having 1-4 carbon atoms optionally substituted with a halogen, a straight or branched chain alkoxy group having 1-4 carbon atoms optionally substituted with a halogen, amino group optionally substituted, nitro group or trifluoromethyl group, or R1 and R2 together denote a lower alkylenedioxy group; R3 denotes 3,4,5,6-tetrahydro-2H-pyran-2-yl group or 1-methoxy-1-methylethyl group, and R4 denotes a straight or branched chain alkyl group having 1-4 carbon atoms or a phenyl group optionally substituted.
The second aspect of this invention relates to a process for producing an acetalsulfonate derivative represented by the above formula (1) which comprises:
(a) a first step of esterifying a mandelic acid derivative represented by the following formula (2) 
wherein R1 and R2 are the same as defined above,
(b) a second step of protecting by an acetal a mandelic ester derivative represented by the following formula (3) obtained in the first step, 
wherein R1 and R2 are the same as defined above and R5 denotes a straight or branched chain alkyl group having 1-4 carbon atoms,
(c) a third step of reducing an acetal derivative represented by the following formula (4) obtained in the second step, 
wherein R1, R2, R3 and R5 are the same as defined above, and
(d) a fourth step of reacting with a sulfonyl chloride derivative an ethanediol derivative represented by the following formula (5) obtained in the third step, 
wherein R1, R2 and R3 are the same as defined above.
The third aspect of this invention relates to a process for producing a styrene oxide derivative represented by the following formula (6) 
wherein R1 and R2 are the same as defined above, which comprises:
(e) a deprotecting step of deprotecting the acetalsulfonate derivative represented by the following formula (1) 
wherein R1, R2, R3 and R4 are the same as defined above, and
(f) an epoxidizing step of epoxidizing a sulfoante derivative represented by the following formula (7) obtained in the above-mentioned deprotecting step, with the aid of a base catalyst, 
wherein R1, R2 and R4 are the same as defined above.
The fourth aspect of this invention relates to a process for producing the styrene oxide derivative represented by the above-mentioned formula (6) from a mandelic acid derivative through serial processes, said styrene oxide derivative being represented by the following formula (6), 
wherein R1 and R2 are the same as defined above, which comprises:
(a) a first step of esterifying a mandelic acid derivative represented by the following formula (2) 
wherein R1 and R2 are the same as defined above,
(b) a second step of protecting by an acetal a mandelic ester derivative represented by the following formula (3) obtained in the above-mentioned first step 
wherein R1 R2 and R5 are the same as defined above,
c) a third step of reducing an acetal derivative represented by the following formula (4) obtained in the above-mentioned second step 
wherein R1, R2, R3 and R5 are the same as defined above,
(d) a fourth step of reacting with a sulfonyl chloride derivative an ethanediol derivative represented by the following formula (5) obtained in the above-mentioned third step 
wherein R1, R2 and R3 are the same as defined above,
(e) a deprotecting step of deprotecting an acetalsulfonate derivative represented by the following formula (1) obtained in the above-mentioned fourth step 
wherein R1, R2, R3 and R4 are the same as defined above, and
(f) an epoxidizing step of epoxidizing a sulfonate derivative represented by the following formula (7) obtained in the above-mentioned deprotecting step, with the aid of a base catalyst 
wherein R1, R2 and R4 are the same as defined above,
Some embodiments of this invention are described further in detail below.
The acetalsulfonate derivative of this invention is represented by the above-mentioned formula (1), wherein R1 and R2 can be same as or different from each other and each denote a hydrogen atom, halogen atom, hydroxyl group, a straight or branched chain alkyl group having 1-4 carbon atoms optionally substituted with a halogen, a straight or branched chain alkoxy groups having 1-4 carbon atoms optionally substituted with a halogen, amino group optionally substituted, nitro group or trifluoromethyl group, or R1 and R2 together denote a lower alkylenedioxy group.
The straight or branched chain alkyl group having 1-4 carbon atoms optionally substituted with a halogen can be, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, trifluoromethyl group. and trichloromethyl group. The straight or branched chain alkoxy group having 1-4 carbon atoms optionally substituted with a halogen can be, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, tert-butoxy group and trifluoromethoxy group. The amino group optionally substituted can be, for example, amino group, methylamino group, dimethylamino group, methylethylaminno group, morpholino group, piperidino group, pyrrolyl group, imidazolyl group and triazolyl group. The halogen atom can be a fluorine, chlorine, bromine or iodine atom. The lower alkylenedioxy group formed conjointly by R1 and R2 together can be, for example, the methylenedioxy group and ethylenedioxy group.
In the above-mentioned formula (1), R3 denotes 3,4,5,6-tetrahydro-2H-pyran-2-yl group or 1-methoxy-1-methylethyl group; R4 denotes a straight or branched chain alkyl group having 1-4 carbon atoms or a phenyl group optionally substituted. The straight or branched chain alkyl group having 1-4 carbon atoms can be, for example, methyl group, and the phenyl group optionally substituted can be, for example, p-tolyl group.
Specific examples of the acetalsulfonate derivative of this invention include 2-phenyl-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-chlorophenyl)-2-(1-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(3-chlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-chlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-methylphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(3-methylpheny)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-methylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-hydroxyphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(3-hydroxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-hydroxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-methoxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(3-methoxyphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(4-methoxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-trifluoromethylphenyl)-21-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(3-trifluoromethylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-trifluoromethylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2-aminophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(3-aminophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-aminophenyl)-2-(1-methoxy-1-methylethyloxy)ethyl methanesulfonate, 2-(2-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(3-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(4-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2,4-dichlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(2,4-difluorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-(3,4-methylenedioxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate, 2-phenyl-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(2-chlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-chlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(4-chlorophenyl)-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(2-methylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-methylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(4-methylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2-hydroxyphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(3-hydroxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(4-hydroxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2-methoxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-methoxyphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(4-methoxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2-trifluoromethylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-trifluoromethylphenyl)-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(4-trifluoromethylphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2-aminophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-aminophenyl)-2-(1-methoxy-1-methylethyloxy)ethyl p-toluenesulfonate, 2-(4-aminophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluene sulfonate, 2-(2-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(3-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(4-nitrophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2,4-dichlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, 2-(2,4-difluorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate, and 2-(3,4-methylenediloxyphenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl p-toluenesulfonate. The above-mentioned acetalsulfonate derivatives can also be respectively optically active substances.
The mandelic acid derivative used as a raw material in this invention is represented by the above-mentioned formula (2), wherein R1 and R2 are the same as defined in the above formula (1).
Specific examples of the mandelic acid derivative defined as described above include mandelic acid, 2-chloromandelic acid, 3-chloromandelic acid, 4-chloromandelic acid, 2-methylmandelic acid, 3-methylmandelic acid, 4-methylmandelic acid, 2-hydroxymandelic acid, 3-hydroxymandelic acid, 4-hydroxymandelic acid, 2-methoxymandelic acid, 3-methoxymandelic acid,: 4-methoxymandelic acid, 2-trifluoromethylmandelic acid, 3-trifluoromethylmandelic acid, 4-trifluoromethylmandelic acid, 2-aminomandelic acid, 3-aminomandelic acid, 4-aminomandelic acid, 2-nitromandelic acid, 3-nitromandelic acid, 4-nitromandelic acid, 2,4-dichloromandelic acid, 2,4-difluoromandelic acid, and 3,4-methylenedioxymandelic acid. The above-mentioned mandelic acid derivatives can also be respectively optically active substances.
The mandelic acid derivative defined as described above can be easily converted, in the first step, into a corresponding mandelic ester derivative represented by the formula (3) by esterification. For example, it can be easily prepared in the presence of an acid catalyst in an alcohol, such as methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, sec-butanol and tert-butanol. In the mandelic ester derivative represented by the formula (3) obtained in the first step, R5 is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl group.
In the esterification of the first step reaction, the alcohol can be used in excess to use it also as a solvent, but organic solvents other than alcohols can also be used. Examples of the organic solvent include aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and tert-butyl methyl ether, ester type solvents such as ethyl acetate and methyl acetate, and nitrile type solvents such as acetonitrile. These organic solvents can be used each alone or as a mixture thereof.
The acid catalyst which can be used in the first step can be, for example, sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, p-toluenesulfonic acid and methanesulfonic acid.
The reaction temperature of the first step can be in the range of: 0-100xc2x0 C., preferably 20xc2x0 C.-80xc2x0 C. The reaction period of time, which can vary according to the acid used and the reaction temperature, can be usually not more than 12 hours, preferably in the range of 0.5-6 hours.
The mandelic ester derivative of the formula (3) obtained in the first step can be easily converted, in the second step, into a corresponding acetal derivative represented by the formula (4), for example, by reacting it with an acetalizing agent under acidic conditions by use of an acid catalyst. In the formula (4), R3 and R5 have the same meaning as described above.
The acetalizing agent which can be used in the second step can be, for example, 1-methoxy-1-methylethyl or 3,4-dihydro-2H-pyran.
The acid catalyst which can be used in the second step can be, for example, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid and methanesulfonic acid.
The reaction solvent which can be used in the second step can be organic solvents inert to the reaction used each alone or as a mixture thereof, for example, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and t-butyl methyl ether, ester type solvents such as ethyl acetate and methyl acetate, and nitrile type solvents such as acetonitrile.
The reaction temperature of the second step can be in the range of 0-100xc2x0 C., preferably 10-40xc2x0 C. The reaction period of time, which can vary according to the acid used and the reaction temperature, can be usually not more than 12 hours, preferably in the range of 0.5-6 hours.
The acetal derivative of the formula (4) obtained in the second step can be easily converted, in the third step, into the corresponding ethanediol derivative represented by the formula (5) by a reduction thereof.
A reducing agent which can be used in the third step can be, for example, sodium borohydride, lithium aluminum hydride and sodium dihydrobis(2-methoxyethoxy)aluminate, preferably sodium dihydrobis(2-methoxyethoxy)aluminate.
A reaction solvent which can be used in the third step can be organic solvents inert to the reaction, used each alone or as a mixture thereof, for example, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and t-butyl methyl ether, ester type solvents such as ethyl acetate and methyl acetate, and nitrile type solvents such as acetonitrile.
A reaction temperature of the third step can be in the range of xe2x88x9220to 100xc2x0 C., preferably 0-40xc2x0 C. A reaction period of time can be usually not more than 12 hours, preferably in the range of 0.5-6 hours.
The ethanediol derivative of the formula (5) obtained in the third step can be easily converted, in the fourth step, into a corresponding acetalsulfonate derivative represented by the formula (1) by reacting it with a sulfonyl chloride derivative.
The sulfonyl chloride derivative used in the fourth step can be, for example, p-toluenesulfonyl chloride and methanesulfonyl chloride.
A base can be used in the fourth step. The base can be, for example, trialkylamines such as trimethylamine and triethylamine, cyclic tertiary amides such as N-methylmorpholine and N-methylpiperidine, N,N-dimethylaniline, pyridine, sodium hydroxide and potassium hydroxide.
A reaction solvent which can be used in the fourth step can be organic solvents inert to the reaction, used each alone or as a mixture thereof, for example, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and t-butyl methyl ether, ester type solvents such as ethyl acetate and methyl acetate, nitrile type solvents such as acetonitrile, and water.
A reaction temperature of the fourth step can be in the range of xe2x88x9220 to 100xc2x0 C., preferably 0-40xc2x0 C. A reaction period of time can be usually not more than 12 hours, preferably in the range of 0.5-6 hours.
The intended acetalsulfonate can be easily purified after a completion of the reaction, according to necessity, for example by using a column.
When optically active mandelic acid derivatives are used as the starting compounds and subjected to reaction by the above-mentioned method, it has been found that the acetalsulfonate derivatives obtained have respective corresponding configurations and thus the configurations have been retained. Thus, it has become possible to provide from an optically active mandelic acid derivative a corresponding optically active acetalsulfonate derivative while retaining the configuration. The optical purity of the optically active acetalsulfonate derivative obtained was determined by high performance liquid chromatography using an optical resolution column.
In the process for producing a styrene oxide derivative of the third aspect of this invention, specific examples of the acetalsulfonate derivative used as the starting material can be the acetalsulfonate derivatives of the first aspect of this invention described above and the acetalsulfonate derivatives obtained by the method of the second aspect of this invention described above.
The protecting step of the step (e) in the third aspect of this invention is a step of deacetalizing the acetalsulfonate derivative represented by the formula (1) of the starting material to form a sulfonate derivative represented by the formula (7). In the step (e), the acetalsulfonate derivative can be easily deprotected, for example, by treating it with an acid.
The acid can be, for example, inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as formic acid, acetic acid, methanesulfonic acid and p-toluenesulfonic acid.
A reaction solvent which can be used in the step (e) can be protic solvents, such as water, methanol, ethanol and isopropanol, used alone or as a mixture thereof with an aprotic solvent. The aprotic solvents used can be, for example, aromatic hydrocarbons such as toluene and xylene, aliphatic hydrocarbons such as hexane, heptane and cyclohexane, halogenated hydrocarbons such as methylene chloride and chloroform, esters such as methyl acetate and ethyl acetate, ethers such as dioxane, tetrahydrofuran, diisopropyl ether and t-butyl methyl ether, and acetonitrile.
A reaction temperature of the step (e) can be 0-100xc2x0 C., preferably 20-80xc2x0 C. A reaction period of time, which can vary according to the acid, solvent and reaction temperature used, can be usually not more than 12 hours, preferably 0.5-6 hours.
The epoxidizing step of the step (f) in the third aspect of this invention is a step of epoxidizing the sulfonate derivative represented by the formula (7) obtained in the step (e) in the presence of a base catalyst.
The base catalyst used can be, for example, alkali metal alcoholates such as sodium methoxide and sodium ethoxide, alkali metal salts such as sodium hydroxide and potassium hydroxide, and alkali carbonates such as sodium carbonate and potassium carbonate.
A reaction solvent which can be used in the step (f) can be protic solvents, such as water, methanol, ethanol and:isopropanol, used each alone or in combination or as a mixture thereof with an aprotic solvent. When an organic solvent immiscible with water is used as a mixture with water, the reaction can be conducted in a double-layer system. The organic solvent immisible with water can be aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as diisopropyl ether and t-butyl methyl ether, and esters such as ethyl acetate and methyl acetate. Examples of organic solvent miscible with water include alcohols such as methanol, ethanol and isopropanol, ethers such as dioxane, tetrahydrofuran and dimethoxyethane, amides such as N,N-dimethylformamide and N,N-dimethylacetamide, and acetonitrile.
A reaction temperature of the step (f) can be in the range of 0-100xc2x0 C., preferably 10-40xc2x0 C. A reaction period of time, which can vary according to the base and reaction temperature used, can be usually not more than 12 hours, preferably 0.5-6 hours.
Specific examples of the styrene oxide derivative represented by the formula (6) obtained by the two steps of step (e) and step (f) from the acetalsulfonate derivative represented by the formula (1) include styrene oxide, 3-chlorostyrene oxide, 4-chlorostyrene oxide, 3,4-dichlorostyrene oxide, 4-methylstyrene oxide, 3,4-methylenedioxystyrene oxide, 4-trifluoromethylstyrene oxide and 2-chlorostyrene oxide. The styrene oxide derivatives mentioned above can also be respectively optically active substances.
It has been found that when optically active acetalsulfonate derivatives are used as the starting compounds and subjected to reaction by the above-mentioned method, the styrene oxide derivatives obtained have respective corresponding configurations and thus the configurations have been retained. Thus, it has become possible to provide from an optically active acetalsulfonate derivative a corresponding optically active styrene oxide derivative while retaining the configuration. The optical purity of the optically active styrene oxide derivative was determined by high performance liquid chromatography using an optical resolution column.
In the process for producing a styrene oxide derivative of the fourth aspect of this invention, wherein the styrene oxide derivative represented by the formula (6) is produced from the mandelic acid derivative represented by the formula (2) through serial processes, the mandelic acid derivative used is the same as that represented by the formula (2) in the second aspect of this invention, the first step of esterifying the mandelic acid derivative is the same as the first step in the second aspect of this invention, the mandelic acid derivative obtained in the first step is the same as that represented by the formula (3) in the second aspect of this invention, the second step of protecting the mandelic acid derivative by an acetal is the same as the second step in the second aspect of this invention, the acetal derivative obtained in the second step is the same as that represented by the formula (4) in the second aspect of this invention, the third step of reducing the acetal derivative is the same as the third step in the second aspect of this invention, the ethanediol derivative obtained in the third step is the same as that represented by the formula (5) in the second aspect of this invention, the fourth step of reacting the ethanediol derivative with a sulfonyl chloride derivative is the same as the fourth step in the second aspect of this invention, the acetalsulfonate derivative obtained in the fourth step is the same as the acetalsulfonate derivative represented by the formula (1) of the first aspect of this invention and the same as the acetalsulfonate derivative obtained by the process of the second aspect of this invention, the: deprotecting step (step (e)) of deprotecting the acetalsulfonate derivative is the same as the step (e) in the third aspect of this invention, the sulfonate derivative obtained in the step (e) is the same as that represented by the formula (7) in the third aspect of this invention, and the epoxidizing step (step (f)) of epoxidizing the sulfonate derivative with the aid of a base catalyst is the same as the step (f) in the third aspect of this invention.